Found programs: Science and Technology Project of Inner Mongolia Autonomous Region ( No . 2021GG0401) ; “Clinical Medicine + X Multidisciplinary ” Joint Research Fund of Baotou Medical College ( No . BYJJ-DXK 2022029)
Authors:Guan Chenjuan1 , Xie Caixia2 , Zheng Xiaojiao2 , Bao Nana2 , Wang Lu2 , Bai Wenhui2 , Qiao Shu2 , Zhang Haonan3
Keywords:breast cancer;astragalus polysaccharide;exosome;macrophage polarization; migration; invasion
DOI:10.19405/j.cnki.issn1000-1492.2025.10.003
〔Abstract〕 To investigate the effects and mechanisms of Astragalus Polysacharin (APS) on the prolifer- ation and metastasis of breast cancer cells by regulating miR-107 and miR-346-mediated macrophage polarization in breast cancer-derived exosomes . Methods Forty 8-week-old female BALB/c mice were selected and breast cancer xenograft models and 4T1 transplanted tumor models were established . The mice were divided into the control group and the APS group . The APS group mice received daily intragastric administration of APS for 25 days , while the control group mice were given the same amount of normal saline . After all treatments were completed , the mice were euthanized , and tumor tissues were isolated . Western blot and flow cytometry were used to detect the expres- sions of proliferating cell nuclear antigen (PCNA) , Ki-67 , CD206 , CD163 , inducible nitric-oxide synthase (iN- OS) , and CD86 . The apoptosis of single-cell suspensions in tumor tissues was analyzed . Human breast cancer cell line MDA-MB-231 was cultured and stimulated with APS , and exosomes from the cell culture medium were collect- ed . The proliferation , migration , and invasion of cells were detected by CCK-8 assay , scratch assay , permeability chamber cell invasion assay , and qRT-PCR . Differentially expressed genes were screened by bioinformatics . Re- sults By measuring the expressions of molecules related to breast cancer cell proliferation and metastasis , it was shown that APS treatment reduced the expressions of proliferation-related proteins (PCNA and Ki-67) and metasta- sis-related proteins (Vimentin) in MDA-MB-231 xenograft tumor tissues; and the polarization of tumor-associated macrophages was observed . APS treatment of 4T1 transplanted tumor tissues could reduce the number of M2 macro- phages and increase the number of M1 macrophages , resulting in a decrease in the ratio of M2/M1 macrophages and an increase in cell apoptosis in 4T1 transplanted tumor tissues . The expressions of related proteins iNOS and CD86 increased , and CD206 and CD163 decreased . After APS treatment , the exosomes produced by MDA-MB- 231 reduced the polarization of M2 macrophages and affected the expressions of miR-107 and miR-346 . Conclusion APS inhibits the polarization of M2 macrophages by regulating the expression of miR-107 or miR-346 in breast cancer cell-derived exosomes , ultimately inhibiting the proliferation and metastasis of breast cancer cells .